Studies will be directed toward learning more about the factors that regulate cardiac protein balance, using fetal mouse hearts in organ culture as the experimental model. The importance of changes in protein degradation as well as protein synthesis will be explored. The cellular mechanisms responsible for protein degradation will be studied, with special emphasis on the possible roles of the lysosomal apparatus and the microtubular apparatus of the cell. In recognition that the mechanisms and regulation of protein balance may be different for different proteins, attention will be focused on the separate assessment of changes in the synthesis and degradation of individual proteins (e.g., myosin) or classes of protein (e.g., organellar vs. cytosolic) during various interventions. Specific studies will include those designed to explore the effects of agents that disrupt the microtubular apparatus; lysosomotropic agents and proteinase inhibitors; hormones; and certain pharmacological agents. Other experiments will be concerned with the role of autophagic vacuole formation in the repair of sublethal cell injury and the changes in protein turnover that accompany this phenomenon. In all studies, correlations will be made between changes in net protein balance, the synthesis and degradation of total protein and of different subclasses of protein, and lysosomal properties as assessed biochemically and anatomically.